Mechanisms by which fibrinogen synthesis is regulated will be investigated. The effects of purified species of fibrinogen-fibrin degradation products upon production of fibrinogen, in vivo and in vitro, will be studied. The presence of bacterial endotoxin in the cerebrospinal fluids of patients with various forms of meningitis will be sought and correlated with other clinical and laboratory measurements. The frequency of thrombocytopenia and other changes in blood coagulation following administration of beef lung or pork mucosal heparin will be determined. Studies of the effects of bacterial endotoxin, present as a contaminant in preparations of other biologically active substances such as concanavalin A and erythropoietin, will be evaluated. Thrombopoietin, obtained from the plasma of thrombocytopenic rabbits, will be further purified using DEAE cellulose and Sephadex as the initial chromatographic steps. Attempts will be made to utilize in vitro cultures of hematopoietic cells for the direct study of the effects of thrombopoietin on megakaryocyte numbers, size, and DNA content.